Technology for rapidly shutting off the production of specific proteins in eukaryotes would be of widespread utility as a research tool and for gene or cell therapy applications, but a simple and effective method has yet to be developed. Controlling protein production through repression of transcription is slow in onset, as existing mRNA molecules continue to be translated into proteins after transcriptional inhibition. RNA interference (RNAi) directly induces mRNA destruction, but RNAi is often only partially effective and can exhibit both sequence-independent and sequence-dependent off-target effects (Sigoillot et al. (2011) ACS Chem Biol 6:47-60). Furthermore, mRNA and protein abundance are not always correlated due to regulation of the translation rate of specific mRNAs (Vogel et al. (2012) Nat Rev Genet 13:227-232; Wu et al. (2013) Nature 499:79-82; Battle et al. (2015) Science 347:664-667). Lastly, both transcriptional repression and RNAi take days to reverse (Liu et al. (2008) J Gene Med 10:583-592; Matsukura et al. (2003) Nucleic Acids Res 31:e77).
Thus, there remains a need for a simple to use system for controlling protein production.